1. Field of the Invention
The present invention generally relates to a taste sensor and a method for manufacturing the same and, more particularly, to a taste sensor using artificial lipid membranes and a method for manufacturing the same.
The present invention relates to an artificial sensor which can replace the five senses of human and, more particularly, to a sensor or an electronic element called a transducer which can replace the sense of taste which is conventionally assumed to be the sense of human which cannot be replaced by an artificial sensor and a taste sensing system using this electronic element.
2. Description of the Related Art
Recently, as scientific techniques have progressed, various types of artificial sensors (transducers) which can perform measurement in place of the five senses of human have been developed.
For example, sensors (a term "transducer" may be more reasonable as a technical term, but a conventional term "sensor" will be used hereinafter) which sense physical amounts such as light, a sound, a temperature, and a pressure corresponding to the senses of sight, hearing, and touch are now available, and some sensors have performance superior to that of human.
Also, as a sensor for sensing a chemical amount such as the type or concentration of a chemical substance corresponding to the sense of smell or taste, an ion-sensitive field effect transistor (ISFET) or an enzyme sensor is known.
Each of these chemical sensors is considered to be characterized by its selectivity, i.e., it responds to only a specific chemical substance. However, an amount to be measured such as a smell or taste to be sensed by human may not be limited to an amount derived from a single substance but may be a combination or mixture of various types of substances. Therefore, it is assumed that realization of a sensor which can totally recognize the smell or taste leads to a sensor close to the five senses of human.
It is assumed that an amount to be measured as a combination or mixture of various types of substances is obtained via a composite effect such as a synergistic effect or a suppression effect between the substances which cause the smell or taste sensation.
Therefore, a smell or taste sensor cannot be realized by a method in which a sensor having selectivity to a specific substance is prepared for each of a plurality of types of substances and signals obtained from these sensors are simply processed by the four rules of arithmetic.
In particular, since an object to be measured by a taste sensor corresponding to the sense of taste must be an amount including a human liking, i.e., a very human factor, it is assumed that the sensor must be arranged to have a structure close to that of a living body.
A taste sensing mechanism (taste receptor mechanism) performed in a living body will be briefly described below. According to Kenzo Kurihara, "Taste", Tokyo University Publishing Society (1978), a biological membrane constituting a receptor cell receives a taste substance in response to a stimulus of the substance, and the membrane potential of the biological membrane changes accordingly. This change generates, via a synapse (a bonding portion between nerve cells called neurones), impulses which propagate in a taste nerve system. The biological membrane is a sensor for converting external information into internal information.
A taste sense organ of a vertebrate is called a taste bud which is a group of several tens of taste cells. Several taste nerves are connected to each taste cell, and a projection called a microvilli is present at the distal end of the taste cell. This projection is assumed to be a portion for receiving a substance eliciting a taste (taste substance). This microvilli membrane is a kind of a biological membrane and consists of lipids and proteins. In the biological membrane, lipids having a polarity form a membrane constituted by a polar bilayer in which hydrophobic portions oppose each other (FIG. 1), and proteins are embedded in proper amount in the polar bilayer.
Referring to FIG. 1, spherical portions indicated by circles represent hydrophilic groups a, and lines extending from the hydrophilic groups (spherical portions) represent chains b of a hydrocarbon. Two chains b extend from each hydrophilic group a in a lipid molecule shown in FIG. 1, and this expression is often used as a method of designing a chemical substance. In general, molecules called a lipid can be schematically illustrated as shown in FIG. 25. Referring to FIG. 25, a rectangle represents a rigid segment.
FIG. 2 shows a mechanism for sensing a taste. Of taste substances, sugar or amino acid which elicits sweetness is assumed to be received by an embedded protein serving as a receptor, and sourness or saltiness is assumed to be adsorbed by a hydrophilic group (whose molecular structure is schematically represented by symbols o in FIG. 2) to change the surface potential of a receptor membrane. A taste substance eliciting bitterness is assumed to be adsorbed by a hydrophobic portion (whose molecular structure is schematically indicated by thin wave forms in FIG. 2) to change the arrangement of the portion or to change an electric charge density, thereby changing the surface potential of the receptor membrane.
In the above description, saltiness, sourness, sweetness, and bitterness are exemplified as four basic tastes in accordance with a classification of physiologists. Mr. Henning uses these four tastes as polar coordinates of corners of a tetrahedron, thereby quantitatively expressing the taste (as if the taste had a shape) in the form of a tetrahedron. This expression is known as a Henning's tetrahedron (FIG. 3).
The present inventors, however, believe on the basis of the recent findings that "Umami" must be considered in addition to the above four tastes. Experimental facts concerning a conventional taste sensor will be briefly described below. According to known references, dioleyl phosphate was used as a lipid molecule, and a sample was prepared by fixing this lipid on a Millipore filter membrane known as a porous filter and used in experiments.
Dioleyl phosphate (DOPH) known as a typical lipid molecule will be described. The formula of DOPH is as follows: ##STR1## =0 and --OH groups at the right side of a phosphorus (P) atom are hydrophilic groups and negatively charged in water. Therefore, these groups attract a hydrogen ion H.sup.+ and a metal ion (e.g., Na.sup.+ in FIG. 2) which cause sourness and saltiness. Two carbon chains extend at the left side of the phosphorus (P) atom in correspondence with the hydrophilic groups (FIG. 2).
When the DOPH molecules are put in an aqueous solution of a salt such as potassium chloride (KCl) or sodium chloride (NaCl), the DOPH molecules are in an oil drop state (as shown at the left side of FIG. 4) if a salt concentration is low. If the salt concentration is increased, alignment gradually progresses to form a bilayer (as shown at the right side of FIG. 4) (this is a kind of phase transition).
The present inventors used a DOPH Millipore membrane prepared by adsorbing DOPH in a polymer cellulose-based support material to examine and experiment an influence of the five basic tastes on a membrane potential, a membrane resistance, and a self-excited oscillation of the membrane and reported partial results in, e.g., the following publications.
(1) MEMBRANE, 12(4), pp. 231 to 237 (1987).
(2) Proc. of the 22nd Jap. Symp. on Taste and Smell (1988), pp. 213 to 216.
(3) Agric. Biol. Chem. 50(11), pp. 2709 to 2714 (1986).
In publication (1), it is reported that the membrane potential and the membrane resistance of a DOPH Millipore membrane differently respond to each of the four basic tastes (saltiness, sourness, bitterness, and sweetness), and self-excited oscillation of the DOPH Millipore membrane independently responds to the four basic tastes.
In publication (2), it is reported that "Umami" is the fifth basic taste and monosodium L-glutamate (MSG), disodium 5'-inosinate (IMP), and disodium 5'-guanylate (GNP) are exemplified as an "Umami" substance. As a result, it is found that a response to "Umami" and a mixture of "Umami" substances synergistically act on a lipid membrane. A synergistic effect is represented by the following equation: EQU y=u+.gamma.uv
where u: the concentration of MSG in a solution, v: the concentration of IMP or GMP to be added to MSG, y: the concentration of an MSG solution which exhibits the same taste strength as that of a solution mixture of the two substances, and .gamma.: a constant for determining the magnitude of the synergistic effect. The constant .gamma. for human is assumed to be represented by the following equations: EQU .gamma.=6.42.times.10.sup.4 (for MSG+IMP] EQU .gamma.=1.48.times.10.sup.5 (for MSG+GMP)
The following values were obtained for the DOPH millipore membrane: EQU .gamma.=6.6.times.10.sup.3 (MSG+IMP) EQU .gamma.=1.0.times.10.sup.4 (MSG+GMP)
That is, it was confirmed that the synergistic effect as a human taste phenomenon could be detected by the lipid membrane.
In publication (3), a suppression effect which is a phenomenon opposite to the synergistic effect was confirmed for a mixture of a salty substance (KCl) and a bitter substance (quinine) since the membrane potential change of the DOPH millipore membrane was reduced.
As described above, according to the initial research by the present inventors, it was found that self-excited oscillation of a DOPH Millipore membrane prepared by adsorbing DOPH in a Millipore membrane having 5 .mu.m pores responds to the taste similarly to the sense of taste of human. These facts suggest that a lipid membrane may detect not only three types of taste substances, i.e., saltiness, sourness, and bitterness but also sweetness and "Umami".
The DOPH Millipore membrane, however, has several problems to be solved to realize its industrial applications. Typical problems are as follows. (1) It is difficult to obtain reproducibility of a measurement result. (2) The membrane cannot be stably used for a long time period. (3) The number of measured quantities obtained from one type of lipid membrane is limited. (4) As a result, only information which is obtained by measurement is unsatisfactory in both quantity and quality.